4-[(morpholinothio)thioxomethyl]morpholine

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Additional information

In a screening/developmental study realised according to the OECD 421 guideline and in compliance with GLP (SafePharm Laboratories 2005, 826/150), rats were exposed in diet with Cure-rite 18 at doses of 0, 60, 200 and 600ppm throughout maturation, mating, gestation and early lactation phases of reproduction. In parental animals, no effects were observed on the epididymides and testes weights and no effects were observed in the number of the corpora lutea of all ovaries from pregnant females or on the number of uterine implantation sites. In offspring, no effect was observed on the number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities. There were no histopathological changes in the tissues examined. There was no effect on offspring viability, growth and development. The No Observed Adverse Effect Level for adults was 600 ppm. The No Observed Effect Level for offspring was 600 ppm.

Short description of key information:

In a screening/developmental study realised according to the OECD 421 guideline and in compliance with GLP (SafePharm Laboratories 2005, 826/150), the NOAEL for adults was 600 ppm. The NOAEL for offspring was 600 ppm.

Effects on developmental toxicity

Additional information

Based on existing data, there is no evidence of reproductive and developmental toxicity. According to the Guidance on Information Requirements and Chemical Safety Assessment (section R7A Reproductive and Developmental toxicity), no further data is required for the assessment of the developmental toxicity of Cure-rite 18.

• In a screening/developmental study realised according to the OECD 421 guideline and in compliance with GLP (SafePharm Laboratories 2005, 826/150), rats were exposed in diet with Cure-rite 18 at doses of 0, 60, 200 and 600ppm throughout maturation, mating, gestation and early lactation phases of reproduction. In parental animals, no effects were observed on the epididymides and testes weights and no effects were observed in the number of the corpora lutea of all ovaries from pregnant females or on the number of uterine implantation sites. In offspring, no effect was observed on the number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities. There were no histopathological changes in the tissues examined. There was no effect on offspring viability, growth and development. The No Observed Adverse Effect Level for adults was 600 ppm. The No Observed Effect Level for offspring was 600 ppm.

• Two separate dominant lethal mutations assays have been realised and showed negative results, suggesting no affection of the germ cells.

The first test was realised according to the OECD 478 guideline and in compliance with GLP (Food And Drug Research Laboratories Inc 1980, 6477). Male rats were treated at doses to 0, 6.25, 12.5 and 25 mg/kg/day during 56 days and were then mating with untreated females. Cure-rite 18 did not alter pregnancy or early fetal deaths. Therefore, Cure-rite 18 is considered to not produce dominant lethal mutations. The second test (Intox Laboratories Inc, 1985, BFG-SC-001) was realised on rat according to a similar protocol at 600ppm in diet. Followed by a mating period to female rats and the mutagenic effects were assessed from the implantation data and mutagenic ratio calculated as a result. Following mating, the female rats were assessed after necropsy and showed that Cure-rite 18 did not cause a significant difference in the implantation efficiencies and mutagenic ratio for each female. This means that Cure-rite 18 is not considered to be mutagenic via the dominant lethal assay.

In conclusion, two tests that evaluate both structural and numerical chromosome aberrations and also dominant lethal effects causing embryonic or foetal death resulting from inherited dominant lethal mutations induced in germ cells of an exposed parent showed a negative results, confirming the absence of effect of Cure-rite 18 on germ cells..

•In a 2 year dietary feeding study Bio/dynamics Inc 1985, 80-2467), no treatment-effects were reported on reproductive organs weight or histology (testes, epididymides, ovaries…).

• Cure-rite 18 is a category 2 carcinogen. Appropriate risk management measures to control exposure are already in place. Emerald Performance Materials recommended exposure threshold limit value for Cure-rite 18 is 0.1 mg/m3, 8-hour TWA.

Justification for classification or non-classification

In a screening/developmental study (OECD 421), no effects were reported in the parental animals or offspring at the highest dose tested (600 ppm).